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A Randomized, Open Label, Multicenter Phase 2 Study, to Evaluate the Efficacy of Sorafenib in Patients With Advanced Renal Cell Carcinoma (RCC) After a Radical Resection of the Metastases

Phase 2
18 Years
Open (Enrolling)
Metastatic Renal Cell Carcinoma

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Trial Information

A Randomized, Open Label, Multicenter Phase 2 Study, to Evaluate the Efficacy of Sorafenib in Patients With Advanced Renal Cell Carcinoma (RCC) After a Radical Resection of the Metastases

Advanced RCC presents poor prognosis, because its pathogenesis is not clearly understood.
However, up-regulation of the Ras pathway is thought to play a role.

VEGF expression could represent independent prognostic factors for survival possibly linking
expression of this protein with clinical outcome.

Sorafenib is a potent inhibitor of both Raf-kinase and VEGF R2 signalling The anti-tumoral
activity of Sorafenib was clearly demonstrated in phase III trial regarding advanced
pretreated RCC.

Surgical removal of metastatic disease could potentially increase the disease control rate.

Particularly in patients with a disease free interval post nephrectomy of at least 1 year,
with one small metastatic lesion, metastasectomy could represents an important therapeutic

After a radical resection of the metastatic disease is unclear if an anti-tumoral systemic
therapy may increase patient survival.

In summary, both the preclinical and clinical data support further evaluation of Sorafenib
in RCC patients.

Inclusion Criteria


- Age ≥ 18 years

- Patients with cytological or histological diagnosis of Renal Cell Carcinoma (RCC)

- Absence of residual lesions following surgical removal of metastatic disease.
Assessment must be performed by CT-scan or MRI

- Histologically proven disease free margins of resected surgical specimen

- No more than three months from radical resection on metastases.

- ECOG Performance Status of 0 or 2

- Life expectancy of at least 12 weeks.

- Adequate bone marrow, liver and renal function as assessed by the following
laboratory requirements to be conducted within 7 days prior to screening:

- Hemoglobin > 9.0 g/dl

- Absolute neutrophil count (ANC) >1,500/mm3

- Platelet count 100,000/ml

- Total bilirubin < 1.5 times the upper limit of normal

- ALT and AST < 2.5 x upper limit of normal (< 5 x upper limit of normal for patients
with liver involvement of their cancer)

- Alkaline phosphatase 4 x ULN

- PT-INR/PTT < 1.5 x upper limit of normal [Patients who are being therapeutically
anticoagulated with an agent such as coumadin or heparin will be allowed to
participate provided that no prior evidence of underlying abnormality in these
parameters exists.] For patients on warfarin, close monitoring of at least weekly
evaluations will be performed, until INR is stable based on a measurement at
pre-dose, as defined by the local standard of care.

- Serum creatinine < 1.5 x upper limit of normal

- Amylase and lipase <1.5 X upper limit of normal

- Signed informed consent must be obtained prior to any study specific procedures


- Prior systemic treatment for metastatic RCC. It is allowed an adjuvant or neoadjuvant
therapy before or after nephrectomy if stopped at least 6 months before the resection
of metastatic lesion/s.

- History of cardiac disease: congestive heart failure >NYHA class 2; active CAD (MI
more than 6 mo prior to study entry is allowed); cardiac arrhythmias requiring
anti-arrhythmic therapy (beta blockers or digoxin are permitted) or uncontrolled
hypertension (>= 160 mmHg systolic and/or 90 mmHg diastolic).

- History of HIV infection or chronic hepatitis B or C

- Active clinically serious infections (> grade 2 NCI-CTC version 3.0)

- Symptomatic metastatic brain or meningeal tumors unless the patient is > 6 months
from definitive therapy, has a negative imaging study within 4 weeks of study entry
and is clinically stable with respect to the tumor at the time of study entry. Also
the patient must not be undergoing acute steroid therapy or taper (chronic steroid
therapy is acceptable provided that the dose is stable for one month prior to and
following screening radiographic studies)

- Patients with seizure disorder requiring medication (such as steroids or

- History of organ allograft

- Patients with evidence or history of bleeding diathesis

- Patients undergoing renal dialysis

- History of other disease, metabolic dysfunction, physical examination finding or
clinical laboratory finding giving reasonable suspicion of a disease condition that
contraindicates use of an investigational drug or patient at high risk from treatment

- Previous or concurrent cancer that is distinct in primary site or histology from the
cancer being evaluated in this study EXCEPT cervical carcinoma in situ, treated basal
cell carcinoma, superficial bladder tumors (Ta, Tis & T1) or any cancer curatively
treated > 3 years prior to study entry.

- Anticancer chemotherapy or immunotherapy during the study or within 4 weeks of study

- Radiotherapy during study or within 3 weeks of start of study drug.

- Major surgery within 4 weeks of start of study

- Autologous bone marrow transplant or stem cell rescue within 4 months of study

- Use of biologic response modifiers, such as G-CSF, within 3 week of study entry.
(G-CSF and other hematopoietic growth factors may be used in the management of acute
toxicity such as febrile neutropenia when clinically indicated or at the discretion
of the investigator, however they may not be substituted for a required dose
reduction.) (Patients taking chronic erythropoietin are permitted provided no dose
adjustment is undertaken within 2 months prior to the study or during the study)

- Investigational drug therapy outside of this trial during or within 4 weeks of study

- Prior exposure to the study drug.

- Pregnant or breast-feeding patients. Women of childbearing potential must have a
negative pregnancy test performed within 7 days of the start of treatment. Both men
and women enrolled in this trial must use adequate barrier birth control measures
during the course of the trial and two weeks after the completion of trial.

- Substance abuse, medical, psychological or social conditions that may interfere with
the patient's participation in the study or evaluation of the study results

- Any condition that is unstable or could jeopardize the safety of the patient and
their compliance in the study

- Patients unable to swallow oral medications

Type of Study:


Study Design:

Allocation: Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Recurrence Free Survival

Outcome Description:

Efficacy of Sorafenib compared with BSC, in RCC patients that have undergone radical resection of recurrent metastatic disease, after prior nephrectomy. The primary efficacy endpoint is Recurrence Free Survival (RFS),

Outcome Time Frame:

December 2011 - December 2014 (3 years)

Safety Issue:


Principal Investigator

Giuseppe Procopio, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Istituto Tumori Milano


Italy: Ministry of Health

Study ID:




Start Date:

December 2011

Completion Date:

September 2016

Related Keywords:

  • Metastatic Renal Cell Carcinoma
  • sorafenib
  • metastatic renal cell carcinoma
  • metastasectomy
  • Carcinoma
  • Carcinoma, Renal Cell
  • Neoplasm Metastasis